PURPOSE: Children with asthma and respiratory failure comprise a small, but significant subset of children with acute asthma. In addition to clinical and historical factors that have been associated with respiratory failure, there may also be genetic factors that predispose some asthmatic children to intubation. However, this has not previously been assessed in this population. We hypothesized that genetic polymorphisms of the β2-adrenergic receptor (ADRβ2) are associated with respiratory failure in children with asthma.
METHODS: We performed genotyping of the ADRβ2 in a pooled cohort of 104 children admitted to the ICU with a severe asthma exacerbation between 2002-2008. Genotype of the ADRβ2 was compared to intubation for respiratory failure.
RESULTS: At amino acid position 16, 33% (n=34) of children were homozygous for the glycine allele (Gly16Gly), 15% (n=16) homozygous for the arginine allele (Arg16Arg), and 52% (n=54) heterozygous (Arg16Arg). At amino acid position 27, 54% (n=56) of children were homozygous for the glutamine allele (Gln27Gln), 8% (n=8) homozygous for the glutamic acid allele (Glu27Glu), and 38% (n=40) heterozygous (Gln27Glu). The haplotypes at these positions were Arg16Gly-Gln27Gln (29%, n=30), Arg16Gly-Gln27Glu (22%, n=23), Gly16Gly-Gln27Glu (16%, n=17), Arg16Arg-Gln27Gln (16%, n=17), Gly16Gly-Gln27Gln (9%, n=9), and Gly16Gly-Glu27Glu (8%, n=8). Twelve children in this cohort were intubated for respiratory failure. Respiratory failure was not associated with age, obesity, race/ethnicity, or NHBLI asthma classification. However, children with the Arg16Gly-Gln27Gln haplotype were significantly more likely to be intubated and mechanical ventilated (OR 4.2; 95% CI 1.2-14.5; p=0.036), than children with other haplotypes of the ADRβ2. When examining the subset of intubated children, those with the Arg16Gly-Gln27Gln haplotype trended toward longer ICU length of stay (329 ± 270 vs 124 ± 57 hours; p=0.09), but this was not statistically significant.
CONCLUSION: Children with the Arg16Gly-Gln27Gln haplotype of the ADRβ2 were 4 times more likely to develop of respiratory failure during severe asthma exacerbations.
CLINICAL IMPLICATIONS: Genetic factors may influence the development of a more severe asthma phenotype during acute exacerbations.
DISCLOSURE: Christopher Carroll, No Financial Disclosure Information; No Product/Research Disclosure Information